Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Stage IV CRC patients have poor prognosis with a five-year survival rate of 14%. Liver metastasis is the main cause of mortality in CRC patients. Since current screening tests have several drawbacks, effective stable non-invasive biomarkers such as microRNA (miRNA) are needed. We aim to investigate the expression of miRNA (miR-21, miR-19a, miR-23a, miR-29a, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345) in the plasma of 62 Lebanese Stage IV CRC patients and 44 healthy subjects using RT-qPCR, as well as to evaluate their potential for diagnosis of advanced CRC and its liver metastasis using the Receiver Operating Characteristics (ROC) curve. miR-21, miR-145, miR-203, miR-155, miR-210, miR-31, and miR-345 were significantly upregulated in the plasma of surgery naïve CRC patients when compared to healthy individuals. We identified two panels of miRNA that could be used for diagnosis of Stage IV CRC (miR-21 and miR-210) with an area under the curve (AUC) of 0.731 and diagnostic accuracy of 69% and liver metastasis (miR-210 and miR-203) with an AUC = 0.833 and diagnostic accuracy of 72%. Panels of specific circulating miRNA, which require further validation, could be potential non-invasive diagnostic biomarkers for CRC and liver metastasis.

Highlights

  • Colorectal cancer (CRC) is the third most common cancer (10.2%) and the second leading cause of cancer death (9.2%) in both sexes worldwide, representing a major health burden [1]

  • Fourteen of the patients were previously diagnosed with CRC at an early stage and had undergone bowel resection surgery and were recently diagnosed with Stage IV CRC

  • We investigated the expression of extensively studied circulating miRNAs in Lebanese Stage IV CRC patients and evaluated their potential to be used as diagnostic biomarkers for advanced CRC and its liver metastasis

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Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer (10.2%) and the second leading cause of cancer death (9.2%) in both sexes worldwide, representing a major health burden [1]. In Lebanon, CRC ranked as the fifth most common cancer accounting for 8% of the newly diagnosed cancer cases over a period of 11 years (2005–2015) [2]. Patients diagnosed with localized and regional CRC (early stage CRC) have a good prognosis with a five-year survival rate reaching 90%. Patients with metastatic CRC (Stage IV CRC) have a five-year survival rate of 14% [3]. Liver metastasis is the main cause of mortality in CRC patients [4]. The 5-year overall survival rates after hepatectomy for colorectal cancer metastasis is improved (47–60% surviving at 5 years), recurrence occurs in 40–75% of patients after liver resection [5]. It would be essential to find more effective, cheap, and noninvasive biomarkers for the early detection of CRC and continuous monitoring of CRC liver metastasis

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